Abstract
Estimates of biological age based on DNA methylation patterns, often referred to as “epigenetic age”, “DNAm age”, have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2×10−9), independent of chronological age, even after adjusting for additional risk factors (p<5.4×10−4), and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5×10−43). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality.
Highlights
DNA methylation-based biomarkers, often referred to as “epigenetic age” or "epigenetic clock", are robust estimators of chronological age of an individual [1,2,3,4]
We showed that the extrinsic measure epigenetic age acceleration (EEAA) out-performs previous measures of age acceleration when it comes to predicting all-cause mortality
This study shows that epigenetic age captures an aspect of biological age, as assessed through lifespan, above and beyond chronological age, blood cell composition, and a host of traditional risk factors of mortality
Summary
DNA methylation-based biomarkers, often referred to as “epigenetic age” or "epigenetic clock", are robust estimators of chronological age of an individual [1,2,3,4]. A measure of epigenetic age based on levels of methylation in 353 CpG dinucleotide markers (cytosine linked to guanine by a phosphate group) allow the estimation of the age of an individual. This estimate is consistent across most types of biological specimens, including whole blood, brain, breast, kidney, liver, lung, and saliva and cell types, including CD4+ T cells, monocytes, B cells, glial cells, and neurons [3]. We recently showed that the offspring of semi-supercentenarians (subjects who reached an age of 105-109 years) have a lower epigenetic age than age-matched controls [8] Based on these findings, it has been hypothesized that epigenetic age captures some aspect of biological age and the resulting susceptibility to disease and multiple health outcomes. A first step in testing this hypothesis is to test whether epigenetic age predicts longevity in multiple populations and across ethnic groups
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